JP2794089B2 - Method for producing alkenylphosphine oxide compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing an alkenylphosphine oxide compound, which comprises reacting a secondary phosphine oxide with an acetylene compound in the presence of a palladium complex catalyst.

Alkenyl phosphine oxides are easily converted to tertiary phosphines by reducing them, and tertiary phosphines are widely used as auxiliary ligands in various catalytic reactions, and therefore are very useful compounds. is there. Further, the compound easily reacts with a nucleophile or a radical species, and can be used for the Horner-Wittig reaction. Therefore, it is a group of compounds having high utility also in synthesizing fine chemicals.

[0003]

2. Description of the Related Art As a method for synthesizing an alkenyl phosphine oxide, a method of reacting an alkenyl Grignard reagent with a phosphorus halide compound and a method of reacting a secondary phosphine oxide with an alkenyl halide have been known. However, the former method involves formation of a magnesium salt. In the latter method, it is necessary to add a base and capture the generated hydrogen halide as a salt. Either method is not industrially preferable in that components not contained in the final product must be used as auxiliary materials.
A method of radically adding a secondary phosphine oxide to an acetylene compound is also known. But,
In this method, a phosphorus atom is introduced at the terminal in the reaction with the terminal acetylene, and an alkenylphosphine oxide having a structure in which a phosphorus atom is introduced into an internal carbon cannot be efficiently obtained.

[0004]

An object of the present invention is to provide a novel method for producing alkenyl phosphine oxide using secondary phosphine oxide as a starting material.

[0005]

Means for Solving the Problems In order to solve the above problems, the present inventors have conducted intensive studies on the reactivity of secondary phosphine oxides with transition metal complexes, and have found that secondary phosphine oxides have low valence complexes. And found that the phosphorus-hydrogen bond could be cleaved, and that the complex thus formed was reactive with acetylene. At that time, it was also found that the presence of phosphinic acid significantly changed regioselectivity. The present invention has been completed based on these facts.

That is, according to the present invention, a compound represented by the general formula

Embedded image (Wherein R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group) An acetylene compound represented by the general formula

Embedded image (Wherein R ³ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group) when reacting a secondary phosphine oxide represented by the general formula:

Embedded image (Wherein, R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group).

Embedded image (Wherein R ¹ , R ² and R ³ have the same meaning as described above). Further, according to the present invention, in the presence of a palladium complex catalyst, the general formula

Embedded image (Wherein R ⁵ and R ⁷ are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group and a silyl group) Represents a group of
R6 is an alkylene group, a cycloalkylene group, an arylene group, heteroarylene group, an aralkylene group, an alkenylene group, alkylenedioxy group, arylene group, divalent selected from the oxaalkylene groups, and O hexa alkylene arylene group A diacetylene compound represented by the general formula:

Embedded image (Wherein R ³ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group) when reacting a secondary phosphine oxide represented by the general formula:

Embedded image (Wherein, R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group).

Embedded image And / or general formula

Embedded image (Wherein, R ³ , R ⁴ , R ⁵ and R ⁶ have the same meaning as described above). A process for producing a bis (alkenylphosphine oxide) compound represented by the formula:

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The secondary phosphine oxide used in the present invention is represented by the general formula (2). In the above formula, R ³ represents an alkyl group, a cycloalkyl group, an aralkyl group, or an aryl. Specific examples of R ³ include a methyl group, an ethyl group, a hexyl group, a cyclohexyl group, a phenyl group, and a benzyl group.

The acetylene compound used in the present invention is represented by the general formula (1). In the above formula, R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group and a silyl group. Represents a group of Another acetylene compound used in the present invention is represented by the general formula (5). Wherein R ⁵ and R ⁷ are a hydrogen atom, an alkyl group,
A monovalent group selected from a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group and a silyl group, and R ⁶ represents an alkylene group, a cycloalkylene group, an arylene A divalent group selected from a group, a heteroarylene group, an aralkylene group, an alkenylene group, an alkylenedioxy group, an arylenedioxy group, an oxaalkylene group and an oxaalkylenearylene group. R ¹ ,
Examples of R ² , R ⁵ and R ⁷ include a hydrogen atom, a methyl group, a propyl group, a benzyl group, a phenyl group, a thienyl group, a 3-butenyl group, an ethoxy group, a phenoxy group, a trimethylsilyl group and the like. Tetramethylene group as R ^5, a phenylene group, thienylene group, ferrocenylene group, phenylenedioxy group and the like. Further, R ¹ , R ² , R ⁵ , R ⁶ and R ⁷ may be further substituted with various substituents. As the acetylene compound suitable for the production method of the present invention, for example, unsubstituted acetylene, butyne, octyne, phenylacetylene, trimethylsilylacetylene, ethynylthiophene, diethynylbenzene, 1,8-nonadine, hexononitrile, 3-butyne-1- Examples include, but are not limited to, all and cyclohexenylacetylene.

The phosphinic acid present in the reaction system of the present invention is represented by the above general formula (3). In the formula, R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group, or an aryl group. In the phosphinic acid of the general formula (3) to be present in the reaction system, R ⁴ may be the same as or different from R ³ in the secondary phosphine oxide of the general formula (2). Is also good. Specific examples of the phosphinic acid include, for example, diphenylphosphinic acid and dimethylphosphinic acid. The amount of the secondary phosphine oxide to be used is not more than equimolar, preferably 0.01 mol per mol of the secondary phosphine oxide.
０．１0.1 mol.

The occurrence of the reaction of the present invention requires the use of a palladium catalyst, and in the absence of a catalyst, no alkenylphosphine oxide is produced. Although various structures can be used as the palladium catalyst, preferred are so-called low-valent palladium complexes, particularly, zero-valent complexes having tertiary phosphine or tertiary phosphite as a ligand. preferable. It is also a preferred embodiment to use an appropriate precursor complex which is easily converted to a zero-valent palladium complex in the reaction system. Furthermore, a tertiary phosphine or a complex containing no tertiary phosphite as a ligand and a tertiary phosphine or a tertiary phosphite are mixed in a reaction system, and a tertiary phosphine or tertiary phosphite is used as a ligand. A preferred embodiment is a method in which a valence palladium complex is generated and used as a catalyst as it is. Various tertiary phosphines and tertiary phosphites can be cited as ligands exhibiting advantageous performance by any of these methods. Illustrative ligands that can be suitably used include triphenylphosphine, diphenylmethylphosphine, phenyldimethylphosphine, trimethylphosphine, triethylphosphine, diphenylcyclohexylphosphine, phenyldicyclohexylphosphine,
1,4-bis (diphenylphosphino) butane, trimethyl phosphite, triphenyl phosphite and the like can be mentioned. Examples of the complex which does not contain tertiary phosphine or tertiary phosphite as a ligand used in combination therewith include bis (benzylideneacetone) palladium, palladium acetate and the like, but are not limited thereto. Examples of the phosphine or phosphite complex preferably used include dimethylbis (triphenylphosphine) palladium, dimethylbis (diphenylmethylphosphine) palladium, dimethylbis (triethylphosphine) palladium, and (ethylene) bis (triphenylphosphine) palladium. And tetrakis (triphenylphosphine) palladium. Further, a divalent complex such as dichlorobis (triphenylphosphine) palladium may be treated with a reducing agent such as butyllithium and used as it is.

The amount of these palladium complexes used may be a so-called catalytic amount, which is generally based on the amount of the acetylene compound.
20 mol% or less is sufficient. In general, the molar ratio of the acetylene compound to the secondary phosphine oxide is preferably 1: 1.
It does not inhibit the occurrence of the reaction. The reaction does not particularly require the use of a solvent, but may be carried out in a solvent if necessary. As the solvent, a hydrocarbon-based or ether-based solvent is generally used. When the reaction temperature is too low, the reaction does not proceed at an advantageous rate, and when the temperature is too high, the catalyst decomposes. Is done. The intermediate of this reaction is sensitive to oxygen, and the reaction is preferably performed in an atmosphere of an inert gas such as nitrogen, argon, or methane. Separation of the purified product from the reaction mixture
It is easily achieved by chromatography, distillation or recrystallization.

[0012]

EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.

Examples 1 to 8 Benzene (C ₆ H ₆ ) or tetrahydrofuran (TH
F) (Example 4 only): 1 mmol of 1-octin and 1 mmol of diphenylphosphine oxide were dissolved in 2 ml, and 0.04 mmol of diphenylphosphinic acid was added thereto. Mol% was added, and the mixture was reacted under a predetermined condition under a nitrogen atmosphere. NM
As a result of analysis by R, formation of 2-octenyldiphenylphosphine oxide was confirmed. The reaction results are summarized in Table 1.

[0014]

[Table 1]

Examples 9 to 16 Using various acetylene compounds, as in Example 1,
The reaction was performed for 3 hours. The formation of alkenylphosphine oxide according to the structure of acetylene was confirmed by NMR. The reaction results are shown in Table 2. However, in Example 16, cis-PdMe ₂ (PPh ₂ M
e) ₂ was used.

[0016]

[Table 2]

Example 17 In Example 4, cis-PdMe ₂ (P
The reaction was carried out in the same manner as in Example 4 except that 2.1 mmol of methyllithium was added to PdCl ₂ (PPh ₃ ) ₂ instead of Ph ₂ Me) ₂ . 2-octenyldiphenylphosphine oxide was produced in a yield of 72%.

Example 18 A reaction was carried out in the same manner as in Example 1 except that the amount of diphenylphosphinic acid was changed to 0.01 mmol, whereby 2-octenyldiphenylphosphine oxide and 1-octenylphosphine oxide were mixed in a ratio of 70:30. The ratio was obtained quantitatively.

[0019]

According to the present invention, an alkenyl phosphine oxide compound useful for synthesizing ligands for fine chemicals such as pharmaceuticals and agricultural chemicals and complex catalysts is converted into an acetylene compound by a second method.
The simple, safe and efficient synthesis can be achieved simply by reacting the secondary phosphine oxide, and the separation and purification thereof are also easy. Therefore, the industrial significance of the present invention is great.

Claims (2)

(57) [Claims] (1) In the presence of a palladium complex catalyst, a compound represented by the general formula: (Wherein R ¹ and R ² are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group, and a silyl group) An acetylene compound represented by the general formula: (Wherein R ³ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group) when reacting a secondary phosphine oxide represented by the general formula: (Wherein R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group), wherein a phosphinic acid represented by the following formula is present: (Wherein, R ¹ , R ² and R ³ have the same meanings as described above). 2. In the presence of a palladium complex catalyst, a compound represented by the general formula: (Wherein R ⁵ and R ⁷ are monovalent selected from a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group, an alkenyl group, an alkoxy group, an aryloxy group and a silyl group) Represents a group of
R ⁶ is an alkylene group, a cycloalkylene group, an arylene group, heteroarylene group, an aralkylene group, an alkenylene group, alkylenedioxy group, arylene group, divalent selected from among oxaalkylene group, and o hexa alkylene arylene group A diacetylene compound represented by the general formula: (Wherein R ³ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group) when reacting a secondary phosphine oxide represented by the general formula: (Wherein R ⁴ represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group), wherein a phosphinic acid represented by the general formula is present: And / or the general formula (Wherein, R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as described above.) A method for producing a bis (alkenylphosphine oxide) compound represented by the formula: